Gametogenesis requires cells to exit from mitosis and undergo the modified cell division program of meiosis to produce differentiated gametes. The shift from mitosis to meiosis and differentiation requires the rewiring of important regulatory circuits in the cell. Sporulation in yeast is a tractable model system in which to study these events. As yeast cells complete meiosis and form spores (gametes) specific histone modifications occur and similar modifications have been reported during gametogenesis in metazoans. Using chromatin immunoprecipitation in combination with tiling microarrays, the distribution of these modified histiones in the chromatin will be defined. Also, the function of these changes with respect to the will be analyzed by phenotypic characterization of spores lacking the modifications and by use of a microscopic assay to assess chromatin condensation in wild-type and mutant spores. Transcription of genes late in sporulation must take place in this altered chromatin context. The interplay between chromatin and a transcription factor necessary for late gene expression will be explored. Meiosis and sporulation occur in response to environmental cues, similar to differentiation in higher cells. Also similar to higher cells, as yeast enter meiosis they pass a commitment point after which, even if the inducing signals are lost or reversed, they nevertheless complete sporulation. As part of this commitment process, the expression of a set of genes important for spore formation becomes insulated from changes in external signals. We will test the hypothesis that these insulated genes represent an autoregulatory gene set and investigate the molecular basis for the insulation of these genes. Whether insulation occurs at the level of transcription or RNA stability will be determined, the cis-acting sequences responsible for insulation will be defined and the protein(s) binding to these seqeunces will be identified.

Public Health Relevance

Gametogenesis, is essential for reproduction and defects can lead to sterility or birth defects in humans. Baker's yeast, Saccharomyces cerevisiae, provides an excellent model system for understanding the process of gametogenesis. This work will explore how the chromosomes are altered during this process and how these changes affect gene expression and the commitment of cells to form gametes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM088297-04
Application #
8451432
Study Section
Special Emphasis Panel (ZRG1-CB-Q)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2013
Total Cost
$284,523
Indirect Cost
$103,251
Name
State University New York Stony Brook
Department
Type
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
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